Taurine for ADHD
Taurine (2-aminoethanesulfonic acid) is a sulfur-containing free β-amino acid. As an aminosulfonic acid, taurine cannot form peptides. Taurine is considered semi-essential in mammals.
A healthy person has 50 to 70 g of taurine in their body.
Taurine has therapeutic significance for1
- ADHD
- neurological developmental disorders
- Angelman syndrome
- Fragile X syndrome
- Sleep-wake disorders
- Neural tube defects
1. Taurine synthesis
Taurine biosynthesis mainly takes place peripherally in the liver via the methionine - cysteine - cysteine sulphonic acid - hypotaurine - taurine pathway.
In the brain, taurine is synthesized in the hippocampus and cerebellum by conversion of the amino acid cysteine by sulfinic acid decarboxylase (taurine synthase and CAD/CSAD).
Taurine can cross the blood-brain barrier. However, unlike all other neuroactive amino acids, taurine consists of sulfonic acid rather than carboxylic acid, which makes it more difficult to cross the blood-brain barrier1
In humans, the rate of taurine biosynthesis in the liver is low, making the diet the most important source of taurine.
Taurine is contained in colostrum (first milk, colostrum, colostrum) as well as usually in infant formula and parenteral solutions.
Cooking does not affect the taurine content. Taurine is found in food
- in large quantities in
- Shellfish, especially mussels, scallops and clams
- dark meat from chickens and turkeys
- some energy drinks (e.g. 1000 mg / 250 ml)
- in small quantities in
- Dairy products.
2. Effects of taurine
Taurine can be found in1
- Brain
- Retina
- Heart
- Placenta
- Leukocytes
- Muscles
Taurine influences signal transmission in the brain. It stimulates the influx and membrane binding of calcium and supports the movement of sodium and potassium through the cell membrane. This increases contraction and has an anti-arrhythmic effect on the heart. As an antioxidant, taurine protects tissue from oxidative damage.23
In the developing brain, the taurine concentration in the first postnatal week is 3-4 times higher than in the adult brain.4
- soothing in relation to
- Consequences of inflammation and oxidative stress
- neurodegenerative diseases
- Stroke
- Epilepsy6
- diabetic neuropathy
- protective in relation to
- modulating / regulating
- Brain development
- Development of the optical system (retina)
- Immune system
- Stress of the endoplasmic reticulum
- Ca2+ homeostasis12
- neuronal activity and excitability at the molecular level
- Learning and memory
- Aggression inhibition
- Energy metabolism
- Gene expression
- Osmosis
- Reproduction
- Stabilization of membranes
- Regulation of the heart muscle
- suppresses the formation of reactive oxygen species13
- inhibits cellular apoptosis14
Whether taurine boosts the metabolism by influencing insulin levels is an open question.
Taurine has a blood pressure-lowering effect.
Taurine and salt can lead to an excessive sodium content in the cells, which can be life-threatening.
According to a statement by the European Food Safety Authority, the NOAEL (No Observed Adverse Effect Level) for taurine is 1000 mg/kg per day.
Taurine influences
- Synapsin 115
- crucial for the development of synapses
- Postsynaptic density protein-95 level15
- crucial for the development of synapses
- Proliferation of stem/progenitor cells16
- increased survival rate of newborn neurons, improved neurogenesis in adulthood
- antidepressant effect and protective effect against mild unpredictable stress, possibly due to17
- Regulation of the HPA stress axis
- Promotion of the formation, survival and growth of neurons in the hippocampus
Offspring of mothers with taurine deficiency show a lower brain weight and abnormal morphologies in the visual cortex18 and in the cerebellum19
Taurine deficiency often correlates with kidney failure and immune system disorders, especially increased inflammation.2
Mice without a functioning taurine transporter (TauT-KO mouse):11
- Loss of long-term potentiation in the striatum20
- impaired GABAergic inhibition in the striatum,21 which can influence anxiety behavior22
- less anxiety-like behavior in the elevated plus maze test23
- Hearing problems2320
- a lower body weight20
- Motion intolerance24
- skeletal muscle atrophy24
- various diseases at an advanced age
- shortened life expectancy1125
- 591 days in TauT-KO mice
- 795 days for non-TauT-KO littermates
A one-week course of taurine significantly reduced the levels of 17 cytokines and increased the level of one:28
- IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17, tumor necrosis factor (TNF)-α, interferon-gamma, eotaxin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, leptin, monocyte chemotactic protein-1 and vascular endothelial growth factor (VEGF) decreased
- Macrophage inflammatory protein 1 alpha increased
Taurine effectively reversed the severity of traumatic brain injury by - Cerebral edema decreased
- the increased activity of the astrocytes reduced
- reduced the proinflammatory cytokines
Taurine tonically activates GABA-A receptors29 in the thalamus.30
Taurine stimulated ERK I/II activity in the presence of AMPA or H2O2.6 This could be relevant for dopamine uptake by DAT and thus for ADHD.
Taurine appears to regulate neurotransmitter actions and the synaptic receptivity of entire brain regions. Taurine could influence the extent to which the respective brain region is capable of neuronal information processing and can regulate behavior. The taurine level in a brain region could serve as an index for the regional reactivity to synaptic input signals and thus for the function of the brain region in question as a whole. Consequences, the observed changes in taurine levels in adult rats that received MPH during adolescence could
can explain the hyperfunction of the dorsal striatum and the correlating hypofunction of the nucleus accumbens.31
3. Taurine for ADHD
We could not find any studies on the effect of orally ingested taurine on extracellular or phasic dopamine.
Taurine injected into the abdominal cavity reduced extracellular dopamine levels in the striatum.32 Intrastriatal infused taurine increased the extracellular dopamine concentration in the striatum, while it was decreased intranigrally.3334
In ADHD, extracellular dopamine is reduced and phasic dopamine is increased. See under ADHD - Disorders of the dopamine system In the Dopamine section in the Neurological aspects chapter. An increase in extracellular dopamine, e.g. through reduced dopamine reuptake or increased DAT efflux, would therefore be helpful.
Taurine has so far only been mentioned in a few reports as a possible ADHD medication.2
A study on rats came to the conclusion that taurine can have positive effects on ADHD.35
- Low dew rates increased
- The DAT in the striatum significantly (only) in WKY rats (a non-ADHD animal model)
- Dopamine uptake in the striatum in both SHR and WKY rats.
- High-dose taurine reduces (only) in SHR rats (which represent an animal model of ADHD-C with hyperactivity)
- The DAT in the striatum significantly
- DAT in the striatum are increased in ADHD
-
Dopamine uptake in the striatum
- Dopamine (re)uptake in the striatum is increased in ADHD
- Interleukin (IL)-1β and C-reactive protein
- The horizontal movement
- The functional connectivity of the hippocampus (also in WKY)
- The mean amplitude of low-frequency fluctuations (0.01-0.08 Hz) (mALFF, mean amplitude of low-frequency fluctuation (mean ALFF)) in the hippocampus on both sides (also in WKY)
- The DAT in the striatum significantly
- Both low and high dew amounts increase
- Significantly increased BDNF levels in the striatum of both SHR and WKY rats
BDNF is reduced in ADHD
- Significantly increased BDNF levels in the striatum of both SHR and WKY rats
High-dose taurine reduced hyperactivity in SHR rats by decreasing inflammatory cytokines and modulating functional brain signaling:36
- WKY with high dew yield
- CRP (C-reactive protein) significantly reduced in serum
-
SHR with low or high dew content
- Interleukin (IL)-1β significantly reduced
- CRP significantly reduced
- WKY and SHR with low dew point
- horizontal locomotion significantly increased
-
SHR with high dew point
- horizontal locomotion significantly reduced compared to SHR control group
- WKY like SHR with high dew point
- functional connectivity (FC) significantly reduced
- mean amplitude of the low-frequency fluctuation (mALFF) in the bilateral hippocampus significantly reduced
-
SHR with low or high dew content
- mALFF significantly reduced compared to SHR control group
In people with ADHD, a small study found that37
- A reduced ALFF
- In the right inferior frontal cortex
- In the cerebellum on both sides
- In the missing
- An increased ALFF
- In the right anterior cingulate cortex
- In the left sensorimotor cortex
- In the brain stem on both sides
In contrast, a very comprehensive study with 985 test subjects found significant differences, but also not in the hippocampus.38 Another small study found no correlation between ALFF and ADHD.39
A high consumption of energy drinks with taurine could represent self-medication. One serious disadvantage is the immense amount of sugar and caffeine in these drinks. At the same time, a significant number of people with ADHD report a very high consumption of sugar and caffeine from the time before their medication was discontinued.
4. Taurine for Parkinson’s disease
Taurine protected dopaminergic cells by inactivating microglia-mediated neuroinflammation:7
Taurine suppressed microglial activation induced by paraquat or maneb. When microglia were reduced, this abolished the dopaminergic neuroprotective effects of taurine.
Taurine suppressed paraquat- or maneb-induced microglial M1 polarization and gene expression of proinflammatory factors.
Taurine inhibited the activation of NADPH oxidase (NOX2) by interfering with the translocation of the cytosolic subunit p47phox and the nuclear factor kappa B (NF-κB) signaling pathway, both of which are key factors in the initiation and maintenance of the microglial M1 inflammatory response.
Jakaria M, Azam S, Haque ME, Jo SH, Uddin MS, Kim IS, Choi DK (2019): Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol. 2019 Jun;24:101223. doi: 10.1016/j.redox.2019.101223. PMID: 31141786; PMCID: PMC6536745. ↥ ↥ ↥ ↥
Jakaria, Azam, Haque, Jo, Uddin, Kim, Choi (2019): Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol. 2019 Jun;24:101223. doi: 10.1016/j.redox.2019.101223. ↥ ↥ ↥
Yeon, Kim (2010): Neuroprotective Effect of Taurine against Oxidative Stress-Induced Damages in Neuronal Cells. Biomolecules & Therapeutics, 18(1), 24-31 (2010) DOI: 10.4062/biomolther.2010.18.1.024 ↥
Benítez-Diaz P, Miranda-Contreras L, Mendoza-Briceño RV, Peña-Contreras Z, Palacios-Prü E (2003): Prenatal and postnatal contents of amino acid neurotransmitters in mouse parietal cortex. Dev Neurosci. 2003 Sep-Oct;25(5):366-74. doi: 10.1159/000073514. PMID: 14614264. ↥
Park E, Park SY, Dobkin C, Schuller-Levis G (2014): Development of a novel cysteine sulfinic Acid decarboxylase knockout mouse: dietary taurine reduces neonatal mortality. J Amino Acids. 2014;2014:346809. doi: 10.1155/2014/346809. PMID: 24639894; PMCID: PMC3929995. ↥
Yeon, J. A., Kim, S. J. (2010): Neuroprotective effect of taurine against oxidative stress-induced damages in neuronal cells. Biomolecules and Therapeutics, 18(1), 24-31. ↥ ↥ ↥
Che Y, Hou L, Sun F, Zhang C, Liu X, Piao F, Zhang D, Li H, Wang Q (2018): Taurine protects dopaminergic neurons in a mouse Parkinson’s disease model through inhibition of microglial M1 polarization. Cell Death Dis. 2018 Apr 1;9(4):435. doi: 10.1038/s41419-018-0468-2. PMID: 29568078; PMCID: PMC5864871. ↥ ↥
Jang H, Lee S, Choi SL, Kim HY, Baek S, Kim Y (2017): Taurine Directly Binds to Oligomeric Amyloid-β and Recovers Cognitive Deficits in Alzheimer Model Mice. Adv Exp Med Biol. 2017;975 Pt 1:233-241. doi: 10.1007/978-94-024-1079-2_21. PMID: 28849459. ↥
Tadros MG, Khalifa AE, Abdel-Naim AB, Arafa HM (2005): Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington’s disease phenotype. Pharmacol Biochem Behav. 2005 Nov;82(3):574-82. doi: 10.1016/j.pbb.2005.10.018. PMID: 16337998. ↥
Howard M, Fischer H, Roux J, Santos BC, Gullans SR, Yancey PH, Welch WJ (2003): Mammalian osmolytes and S-nitrosoglutathione promote Delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) protein maturation and function. J Biol Chem. 2003 Sep 12;278(37):35159-67. doi: 10.1074/jbc.M301924200. PMID: 12837761. ↥
Ito T, Yoshikawa N, Inui T, Miyazaki N, Schaffer SW, Azuma J (2014): Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice. PLoS One. 2014 Sep 17;9(9):e107409. doi: 10.1371/journal.pone.0107409. PMID: 25229346; PMCID: PMC4167997. ↥ ↥ ↥
Schaffer SW, Lombardini JB, Azuma J (2000): Interaction between the actions of taurine and angiotensin II. Amino Acids. 2000;18(4):305-18. doi: 10.1007/pl00010320. PMID: 10949914. ↥
Schaffer SW, Azuma J, Mozaffari M (2009): Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol. 2009 Feb;87(2):91-9. doi: 10.1139/Y08-110. PMID: 19234572. REVIEW ↥
Takatani T, Takahashi K, Uozumi Y, Shikata E, Yamamoto Y, Ito T, Matsuda T, Schaffer SW, Fujio Y, Azuma J (2004): Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome. Am J Physiol Cell Physiol. 2004 Oct;287(4):C949-53. doi: 10.1152/ajpcell.00042.2004. PMID: 15253891. ↥
Shivaraj MC, Marcy G, Low G, Ryu JR, Zhao X, Rosales FJ, Goh EL (2012): Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain. PLoS One. 2012;7(8):e42935. doi: 10.1371/journal.pone.0042935. PMID: 22916184; PMCID: PMC3423436. ↥ ↥
Gebara E, Udry F, Sultan S, Toni N (2015): Taurine increases hippocampal neurogenesis in aging mice. Stem Cell Res. 2015 May;14(3):369-79. doi: 10.1016/j.scr.2015.04.001. PMID: 25889858. ↥
Wu GF, Ren S, Tang RY, Xu C, Zhou JQ, Lin SM, Feng Y, Yang QH, Hu JM, Yang JC (2017): Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats. Sci Rep. 2017 Jul 10;7(1):4989. doi: 10.1038/s41598-017-05051-3. PMID: 28694433; PMCID: PMC5504064. ↥
Palackal T, Moretz R, Wisniewski H, Sturman J (1986): Abnormal visual cortex development in the kitten associated with maternal dietary taurine deprivation. J Neurosci Res. 1986;15(2):223-39. doi: 10.1002/jnr.490150212. PMID: 2421007. ↥
Sturman JA, Moretz RC, French JH, Wisniewski HM (1985): Taurine deficiency in the developing cat: persistence of the cerebellar external granule cell layer. J Neurosci Res. 1985;13(3):405-16. doi: 10.1002/jnr.490130307. PMID: 3989883. ↥
Warskulat U, Heller-Stilb B, Oermann E, Zilles K, Haas H, Lang F, Häussinger D (2007): Phenotype of the taurine transporter knockout mouse. Methods Enzymol. 2007;428:439-58. doi: 10.1016/S0076-6879(07)28025-5. PMID: 17875433. REVIEW ↥ ↥ ↥ ↥ ↥
Sergeeva OA, Fleischer W, Chepkova AN, Warskulat U, Häussinger D, Siebler M, Haas HL. GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition. J Physiol. 2007 Dec 1;585(Pt 2):539-48. doi: 10.1113/jphysiol.2007.141432. PMID: 17962336; PMCID: PMC2375488. ↥
Sergeeva OA, Fleischer W, Chepkova AN, Warskulat U, Häussinger D, Siebler M, Haas HL (2007): GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition. J Physiol. 2007 Dec 1;585(Pt 2):539-48. doi: 10.1113/jphysiol.2007.141432. PMID: 17962336; PMCID: PMC2375488. ↥
Watanabe M, Ito T, Fukuda A (2022): Effects of Taurine Depletion on Body Weight and Mouse Behavior during Development. Metabolites. 2022 Jul 9;12(7):631. doi: 10.3390/metabo12070631. PMID: 35888755; PMCID: PMC9318136. ↥ ↥
Warskulat U, Flögel U, Jacoby C, Hartwig HG, Thewissen M, Merx MW, Molojavyi A, Heller-Stilb B, Schrader J, Häussinger D (2004): Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J. 2004 Mar;18(3):577-9. doi: 10.1096/fj.03-0496fje. PMID: 14734644. ↥ ↥ ↥
Ito T, Kimura Y, Uozumi Y, Takai M, Muraoka S, Matsuda T, Ueki K, Yoshiyama M, Ikawa M, Okabe M, Schaffer SW, Fujio Y, Azuma J. Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol. 2008 May;44(5):927-37. doi: 10.1016/j.yjmcc.2008.03.001. PMID: 18407290. ↥ ↥
Heller-Stilb B, van Roeyen C, Rascher K, Hartwig HG, Huth A, Seeliger MW, Warskulat U, Häussinger D (2002): Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. FASEB J. 2002 Feb;16(2):231-3. doi: 10.1096/fj.01-0691fje. PMID: 11772953. ↥
Warskulat U, Borsch E, Reinehr R, Heller-Stilb B, Mönnighoff I, Buchczyk D, Donner M, Flögel U, Kappert G, Soboll S, Beer S, Pfeffer K, Marschall HU, Gabrielsen M, Amiry-Moghaddam M, Ottersen OP, Dienes HP, Häussinger D (2006): Chronic liver disease is triggered by taurine transporter knockout in the mouse. FASEB J. 2006 Mar;20(3):574-6. doi: 10.1096/fj.05-5016fje. PMID: 16421246. ↥
Su Y, Fan W, Ma Z, Wen X, Wang W, Wu Q, Huang H (2014): Taurine improves functional and histological outcomes and reduces inflammation in traumatic brain injury. Neuroscience. 2014 Apr 25;266:56-65. doi: 10.1016/j.neuroscience.2014.02.006. PMID: 24530657. ↥
Furukawa T, Yamada J, Akita T, Matsushima Y, Yanagawa Y, Fukuda A (2014): Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex. Front Cell Neurosci. 2014 Mar 28;8:88. doi: 10.3389/fncel.2014.00088. PMID: 24734001; PMCID: PMC3975117. ↥
Jia F, Yue M, Chandra D, Keramidas A, Goldstein PA, Homanics GE, Harrison NL (2008): Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus. J Neurosci. 2008 Jan 2;28(1):106-15. doi: 10.1523/JNEUROSCI.3996-07.2008. PMID: 18171928; PMCID: PMC6671153. ↥
Marco EM, Adriani W, Ruocco LA, Canese R, Sadile AG, Laviola G (2011): Neurobehavioral adaptations to methylphenidate: the issue of early adolescent exposure. Neurosci Biobehav Rev. 2011 Aug;35(8):1722-39. doi: 10.1016/j.neubiorev.2011.02.011. PMID: 21376076. REVIEW ↥
Salimäki J, Scriba G, Piepponen TP, Rautolahti N, Ahtee L (2003): The effects of systemically administered taurine and N-pivaloyltaurine on striatal extracellular dopamine and taurine in freely moving rats. Naunyn Schmiedebergs Arch Pharmacol. 2003 Aug;368(2):134-41. doi: 10.1007/s00210-003-0776-6. PMID: 12898127. ↥
Ruotsalainen M, Heikkilä M, Lillsunde P, Seppälä T, Ahtee L (1996): Taurine infused intrastriatally elevates, but intranigrally decreases striatal extracellular dopamine concentration in anaesthetised rats. J Neural Transm (Vienna). 1996;103(8-9):935-46. doi: 10.1007/BF01291784. PMID: 9013387. ↥
Ruotsalainen M, Ahtee L (1996): Intrastriatal taurine increases striatal extracellular dopamine in a tetrodotoxin-sensitive manner in rats. Neurosci Lett. 1996 Jul 19;212(3):175-8. doi: 10.1016/0304-3940(96)12821-4. PMID: 8843101. ↥
Chen VC, Chiu CC, Chen LJ, Hsu TC, Tzang BS. Effects of taurine on striatal dopamine transporter expression and dopamine uptake in SHR rats. Behav Brain Res. 2018 Aug 1;348:219-226. doi: 10.1016/j.bbr.2018.04.031. PMID: 29694913. ↥
Chen VC, Hsu TC, Chen LJ, Chou HC, Weng JC, Tzang BS (2017): Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats. PLoS One. 2017 Jul 10;12(7):e0181122. doi: 10.1371/journal.pone.0181122. Erratum in: PLoS One. 2017 Dec 19;12 (12 ):e0190203. PMID: 28700674; PMCID: PMC5507323. ↥
Zang, He, Zhu, Cao, Sui, Liang, Tian, Jiang, Wang (2007) Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev. 2007 Mar;29(2):83-91. ↥
Tang, Wei, Zhao, Zhang, Nie (2017): Abnormal Brain Activity in ADHD: A Study of Resting-State fMRI. In: Zeng, He, Kotaleski, Martone, Xu, Peng, Luo (Hrsg) (2017): Brain Informatics: International Conference, BI 2017, Beijing, China, November 16-18, 2017, Proceedings, Seite 181 ff n = 985 ↥
An, Cao, Sui, Sun, Zou, Zang, Wang (2013): Local synchronization and amplitude of the fluctuation of spontaneous brain activity in attention-deficit/hyperactivity disorder: a resting-state fMRI study. Neurosci Bull. 2013 Oct;29(5):603-13. doi: 10.1007/s12264-013-1353-8. ↥